Methods for three dimensional reconstruction and determining the quality of an embryo

a three-dimensional reconstruction and embryo technology, applied in the field of reproductive medicine, can solve problems such as failure of implantation, complete disappointment, and limitations to predict success

Active Publication Date: 2020-04-21
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to a method for non-invasive 3D reconstruction and 3D printing of human oocytes and embryos for improved evaluation and selection purposes. The method uses standard optical microscopic sections and advanced 3D technologies to obtain high-quality 3D reconstructions and printings, which can be used for optimizing embryo selection and increasing the success rate of assisted reproduction technologies (ART). The method also allows for the assessment of the ability of an oocyte or embryo to perform successfully in terms of pregnancy rate and healthy person formation. By avoiding the transfer in uterus of embryos with poor potential for pregnancy outcome, the method helps embryologists to select the competent oocyte and embryo and reduces the incidence of multiple pregnancies.

Problems solved by technology

This morphological approach is based exclusively on subjective observations of embryo morphology, dependent operator and shows limitations to predict successful pregnancy in ART (Guerif et al., 2007).
Indeed, currently, 85% of embryos obtained in vitro and selected for replacement on morphological criteria lead to implantation failures.
This result is completely disappointing and suggests that the limited 2D-visualization of human oocyte and embryo with optical microscopy lacks accuracy.
Nevertheless, time-lapse systems do not improve embryo morphology evaluation compared to optical microcopy since embryos contained in individual wells are observed only in 7 focal planes.
Indeed, a major limitation of these systems is the inability to rotate or roll spherical oocyte and embryos making it difficult to assess morphology especially in the case of a high fragmentation rate or blastocyst stage.
Indeed, it seems very difficult to analyze in detail a spherical biological structure, such as human oocyte and embryo, only in 2D-planes.
Nowadays, one of the challenges of the optical imaging is to observe in 3D the biological structures and organisms in compatible conditions for the pursuit of their development.
Furthermore, several research teams have proposed an atlas book containing 3D mouse embryo reconstructions using magnetic resonance imaging but most of the time, they did not studied embryos at the early stages.
The use of micro magnetic resonance imaging (μMRI) for 3D human oocyte and embryo reconstruction could be also an attractive way for oocyte and embryo morphology assessment, but nowadays, the image spatial resolution is not sufficient even at high field (even at 9.4 T).

Method used

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  • Methods for three dimensional reconstruction and determining the quality of an embryo
  • Methods for three dimensional reconstruction and determining the quality of an embryo
  • Methods for three dimensional reconstruction and determining the quality of an embryo

Examples

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example 1

[0068]Embryoscan.

[0069]The present invention relates to the methods for three dimensional (3D) reconstruction and 3D printing of human oocytes and embryos. More precisely, it pertains to the use of 3D technologies as new and innovative tools to improve oocyte and embryo morphology assessment during their preimplantation development in vitro.

[0070]The present invention is based on 3D reconstruction and 3D printing of human oocytes and embryos. These 3D technologies can be used for assessing embryo morphology and improving embryo selection in order to increase ART success. Moreover, 3D technologies represent an informative tool for training, updating of embryologist staff and for patients undergoing ART procedure.[0071]This invention comprises the steps consisting of:[0072]i) Providing serially image sections of human oocyte and embryo from standard optical microscopy or light sheet microscopy (for example SPIM) or Optical Coherence Tomography (OCT) or Magnetic Resonance Micro Imaging...

example 2

[0094]Example of a microscope using like sheet based on SPIM. An optical device (1) produces a light sheet (2), illumining a single plane of the object (4). Two objectives (3), placed at 90° relative to the light sheet beam, are each connected to CCD cameras. A computer receives the images from the two cameras and pilots automatically the displacements of the motorized xyz stage (5) to make stacks of pictures of the different planes of the embryo alternatively illuminated by the SPIM. The pictures are finally sent into a visualization software: it mixes the pictures of the two cameras and shows the result in Multiplanar Reconstruction (MPR) and 3D (VR) (FIG. 4).

example 3

[0095]In Vitro Fertilization, Embryo Quality Classification and IVF Outcomes.

[0096]Ovulation is induced by a single injection of 250 μg of human chorionic gonadotropin (OVITRELLE®; Merck Serono). Oocyte retrieval is performed by transvaginal ultrasound-guided aspiration 36 hours after the injection and each pre-ovulatory follicle is aspirated individually without flushing.

[0097]Cumulus-oocyte complexes are isolated for conventional IVF or ICSI procedures. Before microinjection for ICSI, oocyte maturity is assessed after denudation. Oocytes are individually cultured in a 30 μl microdroplet of culture medium (VITROLIFE®) under oil at 37° C. in 6% CO2 and humid atmosphere. Normal fertilization is confirmed by the presence of two pronuclei and two polar bodies 18 to 20 hours after microinjection or insemination. Early cleavage is observed at 25 or 27 hours after microinjection or insemination, respectively.

[0098]Three days after oocyte retrieval, embryo quality is graded from 1 to 4, ac...

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Abstract

The present invention relates generally to the fields of reproductive medicine. More specifically, the present invention relates to methods and devices for determining the quality of an embryo. More specifically, the present invention relates to the use of three dimensional reconstructions for determining the quality of an embryo.

Description

FIELD OF THE INVENTION[0001]The present invention relates generally to the field of reproductive medicine. More specifically, the present invention relates to methods and devices for determining the quality of an embryo.BACKGROUND OF THE INVENTION[0002]Currently, embryo selection for transfer relies on morphological criteria evaluation with optical microscopy in Assisted Reproductive Technology (ART). The parameters classically involved in embryo selection are: i) morphology and fertilization of oocyte having generated embryo, ii) number and size of blastomeres, iii) cytoplasmic appearance of blastomeres, iv) fragmentation rate and v) multinucleation presence. This morphological approach is based exclusively on subjective observations of embryo morphology, dependent operator and shows limitations to predict successful pregnancy in ART (Guerif et al., 2007). Indeed, currently, 85% of embryos obtained in vitro and selected for replacement on morphological criteria lead to implantation...

Claims

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Application Information

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Patent Type & AuthorityPatents(United States)
IPC IPC(8): A61B17/435G06T7/00G06T19/00C12N5/073G06T11/00
CPCA61B17/435G06T7/0014C12N5/0604G06T7/0012G06T11/003G06T19/00G06T2207/30044G06T2207/10101G06T2210/41G06T2207/10056G06T2207/10088A61P15/00
InventorHAMAMAH, SAMIRSCALICI, ELODIE
OwnerINST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)